While normal cells produce ATP via oxidative phosphorylation and rarely produce lactic acid, cancer cells produce ATP via glycolysis and lactic acid fermentation. Accordingly, unlike normal cells, cancer cells require a higher amount of glucose, and glucose is converted by a pro-oncogenic metabolism which prefers glycolysis even in an aerobic environment (Warburg effect). Cancer cells utilize such a metabolic pathway as a major source of energy supply for producing energy sources, and as such, cancer cells create an environment in which survival, proliferation, angiogenesis, and metastasis can occur actively, and progress into a malignant tumor. Therefore, the inhibition of the energy metabolism by cancer cells will increase the likelihood of solving the narrow therapeutic ranges of existing targeted cancer drugs and resistance thereof, and interests have recently been focused on the development of anticancer drugs targeting the metabolic characteristics of these cancer cells (Nature Review cancer 2011; 11: 85-95).
The biguanide-based drugs such as phenformin and metformin are known as mitochondrial complex 1 inhibitor, and these drugs are known to inhibit differentiation and survival of cancer cells by increasing the energy stress of the cancer cells via inhibition of their oxidative phosphorylation. However, the efficacies of these drugs are not strong enough and thus it is difficult for them to be developed into anticancer drugs. In the case of phenformin, a biguanide-based drug, its use has been fully prohibited since the late 1970s due to the side-effect of severe lactic acidosis. Accordingly, there is a need to develop a biguanide-based material with improved physicochemical properties exhibiting excellent pharmacological actions compared to the existing metformin while not exhibiting any side-effects, as in phenformin.